Lung cancer 

About: Lung cancer is an academic journal published by Dove Medical Press. The journal publishes majorly in the area(s): Medicine & Internal medicine. It has an ISSN identifier of 1179-2728. It is also open access. Over the lifetime, 653 publications have been published receiving 614 citations. The journal is also known as: Journal of lung cancer : targets and therapy & Lung cancer, targets and therapy.

Antibody-drug conjugates: A promising novel therapeutic approach in lung cancer

Abstract: Antibody-drug conjugates (ADCs) are rapidly establishing their place and have shown promising preliminary data in lung cancer with impressive response rates and survival outcomes in previously treated patients.There are several ADCs currently in clinical trials for NSCLC and small cell lung cancer (SCLC). These ADCs often have different targets which include HER2, HER3, TROP2, CEACAM5, and MET in NSCLC and DLL3 in SCLC.Here we review the safety, and efficacy of newer ADCs in lung cancer including ado-trastuzumab emtansine, trastuzumab deruxetecan, patritomab deruxetecan, datopotamab deruxetecan, sacituzumab govitecan, SAR408701, Telisotuzumab vedotin, rovalpituzumab tesirine, lorvotuzumab mertansine, and sacituzumab govitecan. Several novel methods are underway to improve the safety and efficacy of ADCs which include increasing the drug to antibody ratio (DAR), the potency of the payload, using more innovative payloads and replacing the antibody.

High dose osimertinib in patients with advanced stage EGFR exon 20 mutation-positive NSCLC: Results from the phase 2 multicenter POSITION20 trial

Abstract: IntroductionPatients with life-threatening advanced non-small cell lung cancer (NSCLC) who harbor an exon 20 deletion and/or insertion mutation (EGFRex20 + ) have limited effective treatment options. The high dose 3rd generation tyrosine kinase inhibitor (TKI) osimertinib shows promising in vitro activity in EGFRex20 + NSCLC tumors.MethodsThe POSITION20 is a single arm phase II, multicenter study investigating 160 mg osimertinib in patients with EGFRex20+, T790M negative NSCLC. We allowed patients to be treatment naïve and to have asymptomatic brain metastases. The primary endpoint was overall response rate (ORR). Secondary outcomes were duration of response (DoR), progression free survival (PFS), overall survival (OS), and treatment related adverse events (trAEs).ResultsFrom June 2018 to October 2021, 25 patients were enrolled across five centers in the Netherlands. The median age was 70 years (range, 47–87), 20 patients (80%) were women, and the median number of previous lines of therapy was 1 (range, 0–3). The exon 20 mutations were clustered between A763 and L777. The most common exon 20 mutations were p.(N771_H773dup) (n = 3) and p.(A767_V769dup) (n = 3). The ORR was 28% (95% CI, 12–49%), including seven partial responses, with a median DoR of 5.3 months (range, 2.7–27.6). The median PFS was 6.8 months (95% CI, 4.6–9.1) and the median OS was 15.2 months (95% CI, 14.3–16.0). The most common trAEs were diarrhea (72%), dry skin (44%), and fatigue (44%). The primary reason for discontinuation was progressive disease in 14 patients (56%).ConclusionThe POSITION20 study showed modest antitumor activity in patients with EGFRex20 + NSCLC treated with 160 mg osimertinib, with a confirmed ORR of 28% and acceptable toxicity.

Biomarker testing and tissue journey among patients with metastatic non-small cell lung cancer receiving first-line therapy in the US Oncology Network biomarker testing in metastatic NSCLC with first-line therapy.

Abstract: The MYLUNG (Molecularly Informed Lung Cancer Treatment in a Community Cancer Network) consortium pragmatic study assessed real-world biomarker testing rates and turnaround times within a large community-based oncology network.This retrospective observational chart review study investigated patients with mNSCLC initiating first-line (1L) systemic therapy between 01-April-2018 and 31-March-2020. Biomarker testing rates and timing relative to 1L therapy for EGFR, ALK, ROS1, BRAF, and PD-L1 were assessed, including use of next-generation sequencing (NGS).Among 3474 adults: 74% had adenocarcinoma and 76% had a documented ECOG performance status of 0 or 1. Ninety percent had testing for at least one biomarker, and 46% received all 5 biomarker tests. Changes in testing rates from 2018 to 2020 were 71% to 71% for EGFR, 71% to 70% for ALK, 69% to 67% for ROS1, 51% to 59% for BRAF, 82% to 84% for PD-L1, and 42% to 49% for all 5 biomarkers. NGS testing increased from 33% to 45% (p < 0.0001). Median time from mNSCLC diagnosis to 1L therapy was 35 days. Median turnaround times from biomarker testing orders to results ranged from 10 to 15 days for the individual biomarkers and 18 days for NGS.In this real-world study, while most patients received at least one biomarker test prior to 1L, <50% received all 5 tests. NGS testing also occurred in < 50% of patients but appeared to increase over time. The next phase of MYLUNG will evaluate contemporary ordering practices and turnaround times prospectively.

Prognostic and predictive value of neutrophil-to-lymphocyte ratio with adjuvant immunotherapy in stage III non-small-cell lung cancer

Abstract: BackgroundElevated pre-treatment neutrophil-to-lymphocyte ratio (NLR) may reflect immune dysfunction and is negatively prognostic in cancer patients treated with immunotherapy, but it is unclear if NLR is predictive of immunotherapy benefit.MethodsWe identified stage III non-small-cell lung cancer (NSCLC) patients treated with definitive chemoradiation and adjuvant durvalumab within the national Veterans Affairs system from 2017 to 2021. We compared the prognostic value of NLR measured before durvalumab start to a control group of stage III NSCLC patients treated with definitive chemoradiation alone from 2015 to 2016 (no-durvalumab group) before the approval of adjuvant durvalumab. We estimated the predictive value of NLR through the statistical interaction of durvalumab group by NLR level. Outcomes included progression-free survival (PFS) and overall survival (OS).ResultsThe primary analysis for NLR included 821 durvalumab patients and 445 no-durvalumab patients. Higher NLR was associated with inferior PFS in both groups (no-durvalumab: adjusted HR [aHR] 1.14 per 7.43 unit increase in NLR, 95% confidence interval [CI] 1.06–1.23; durvalumab: aHR 1.42, 95% CI 1.23–1.64), though this effect was greater in durvalumab patients (p for interaction = 0.009). Similar results were found for OS (no-durvalumab: aHR 1.16, 95% CI 1.09–1.24; durvalumab: aHR 1.48, 95% CI 1.25–1.76; p for interaction = 0.010). Absolute lymphocytes, eosinophils, and basophils were not prognostic in either group. Estimates of durvalumab treatment efficacy suggested declining efficacy with higher NLR.ConclusionPre-treatment NLR is especially prognostic among stage III NSCLC patients treated with adjuvant immunotherapy compared to control patients treated without immunotherapy and may be a predictive biomarker of immunotherapy benefit.

Clinical validation of Guardant360 CDx as a blood-based companion diagnostic for sotorasib

Abstract: Effective therapy for non-small-cell lung cancer (NSCLC) depends on morphological and genomic classification, with comprehensive screening for guideline-recommended biomarkers critical to guide treatment. Companion diagnostics, which provide robust genotyping results, represent an important component of personalized oncology. We evaluated the clinical validity of Guardant360 CDx as a companion diagnostic for sotorasib for detection of KRAS p.G12C, an important oncogenic NSCLC driver mutation.KRAS p.G12C was tested in NSCLC patients from CodeBreaK100 (NCT03600833) in pretreatment plasma samples using Guardant360 CDx liquid biopsy and archival tissue samples using therascreen® KRAS RGQ polymerase chain reaction (PCR) kit tissue testing. Matched tissue and plasma samples were procured from other clinical trials or commercial vendors, and results were compared. Demographics and clinical characteristics and objective response rate (ORR) were evaluated.Of 126 CodeBreaK patients, 112 (88.9%) were tested for KRASp.G12C mutations with Guardant360 CDx. Among 189 patients in the extended analysis cohort, the positive and negative percent agreement (95% CI) for Guardant360 CDx plasma testing relative to therascreen® KRAS RGQ PCR kit tissue testing were 0.71 (0.62, 0.79) and 1.00 (0.95, 1.00), respectively; overall percent agreement (95% CI) was 0.82 (0.76, 0.87). TP53 co-mutations were the most common regardless of KRAS p.G12C status (KRAS p.G12C-positive, 53.4%; KRAS p.G12C-negative, 45.5%). STK11 was co-mutated in 26.1% of KRAS p.G12C-positive samples. The ORR was similar among patients selected by plasma and tissue testing.Comprehensive genotyping for all therapeutic targets including KRAS p.G12C is critical for management of NSCLC. Liquid biopsy using Guardant360 CDx has clinical validity for identification of patients with KRASp.G12C-mutant NSCLC and, augmented by tissue testing methodologies as outlined on the approved product label, will identify patients for treatment with sotorasib.